tbuckley/cabot-search huggingface dataset:
Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Analysis of progression after first subsequent therapy in KEYNOTE-426.
Authors: Thomas Powles, Elizabeth R. Plimack, Viktor Stus, Tom Waddell, Rustem Gafanov, Frédéric Pouliot, Dmitry Nosov, Bohuslav Melichar, Denis Soulieres, Delphine Borchiellini, Ihor Vynnychenko, Raymond S. McDermott, Sergio Jobim Azevedo, Satoshi Tamada, Anna Kryzhanivska, Chenxiang Li, Joseph E. Burgents, L. Rhoda Molife, Brian I. Rini, Jens Bedke
Journal: Journal of Clinical Oncology (2022)

4513 Background: The randomized, open-label, phase 3 KEYNOTE-426 study (NCT02853331) met its primary and key secondary end points of improved OS, PFS, and ORR with pembro + axi versus sunitinib as first-line treatment for patients with advanced ccRCC. Extended follow-up (42.8-mo median follow-up) continued to show the superior efficacy of pembro + axi versus sunitinib in this patient population. We describe the results of PFS2 for all randomly assigned patients and across IMDC risk categories. Methods: Treatment-naive patients with advanced ccRCC, Karnofsky Performance Status Scale score ≥70% and measurable disease per RECIST v1.1 were randomly assigned 1:1 to receive pembro 200 mg IV every 3 weeks for up to 35 doses (̃2 y) + axi 5 mg orally twice daily or sunitinib 50 mg orally once daily on a 4-wk on/2-wk off schedule. The end point of this exploratory analysis was PFS2, defined as time from randomization to progression after first subsequent therapy or any-cause death. The Kaplan-Meier method was used to estimate PFS2 and hazard ratios were estimated using a Cox regression model. Results: Of 861 patients, 432 were assigned to receive pembro + axi; 429, to sunitinib. Median time from randomization to the database cutoff date (January 11, 2021) was 42.8 mo (range, 35.6-50.6). Overall, 47.2% of patients (204/432) in the pembro + axi arm and 65.5% of patients (281/429) in the sunitinib arm received ≥1 line of subsequent anticancer therapy. For patients who received subsequent therapy, anti–PD-1/PD-L1 agents were the first subsequent treatment for 11.3% of patients (23/204) in the pembro + axi arm and 54.8% of patients (154/281) in the sunitinib arm. In the pembro + axi arm, 82.8% of patients (169/204) received a VEGF/VEGFR inhibitor as first subsequent therapy, as did 43.4% (122/281) in the sunitinib arm. PFS2 results are displayed in the Table. Conclusions: In this exploratory analysis, PFS2 was longer for patients randomized to pembro + axi compared to sunitinib. Results were consistent across IMDC risk groups. These data support use of pembro + axi for the first-line treatment of patients with advanced ccRCC. Clinical trial information: NCT02853331. [Table: see text]
Racial concordance and trust in health communications: A randomized trial of videos about prostate cancer.
Authors: Stacy Loeb, Joseph Ravenell, Scarlett Lin Gomez, Hala Borno, Katherine Siu, Tatiana Sanchez Nolasco, Nataliya Byrne, Godfrey Wilson, Derek Griffith, Rob Crocker, Robert Sherman, Aisha Langford
Journal: Journal of Clinical Oncology (2022)

5014 Background: Black men have a significantly higher risk of prostate cancer and more aggressive disease compared to White men. The Internet is a popular source of health information and is commonly used by Black adults. However, Black adults are underrepresented in online content about prostate cancer. Given that medical mistrust is greater among Black compared to White adults, this study sought to evaluate the association between racial representation in online content about prostate cancer and trust in the content. A secondary objective was to identify additional attributes that influence trust in online content. Methods: This was a randomized trial of 2904 U.S. adults age ≥40. Participants were randomly assigned to view one of 8 different online videos. Videos used an equivalent script about either prostate cancer screening or clinical trials presented by one of 4 different presenters: Black physician, Black patient, White physician, or White patient. The primary outcome of the study was trust in the information using a Likert scale. Logistic regression models were applied to compare trust in the videos, based upon the characteristics of the speaker and topic of the video. Results: Study participants were 1703 (59%) Black and 1201 (41%) White adults. Black adults were 1.5 times more likely to trust a Black presenter compared to a White presenter (p&lt;0.001). For White adults, no significant difference in trust was identified between Black or White presenters (p=0.21). For both Black and White adults, a physician presenting the information was more trusted than a patient, and videos discussing screening were more likely to be trusted than those discussing clinical trials (Table). Conclusions: Racial concordance is significantly associated with trust in prostate cancer information among Black adults. Additionally, health information is considered more trustworthy when delivered by a physician. These results highlight the importance of physicians in disseminating health information to the public, and of increasing racial diversity among healthcare providers. They also suggest an ongoing need for public education about clinical trials to prioritize issues of mistrust and distrust. [Table: see text]
Responses to immune checkpoint inhibition among MSI-H pancreatic ductal adenocarcinoma: A multi-institutional case series.
Authors: Tucker Coston, Jason S. Starr, Bassam Bassam Sonbol, Hani M. Babiker, Amit Mahipal, Sakti Chakrabarti, Robert R. McWilliams, Tanios S. Bekaii-Saab, Aakash Desai, Jeremy Clifton Jones, Wen Wee Ma
Journal: Journal of Clinical Oncology (2022)

4145 Background: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer death. Outcomes remain poor, due to irresectability at diagnosis for many and sub-optimal responses to systemic therapy. Cytotoxic chemotherapy remains the standard of care. High microsatellite instability (MSI-H) predicts response to immune checkpoint inhibition (ICI) in many cancers. Detecting high MSI is rare in PDAC (incidence &lt;2%), but case reports demonstrate potential therapeutic benefit with ICI. Here, we present multi-institutional data to characterize the clinical behavior of MSI-H PDAC, with special attention to response to ICI. Methods: Cases of MSI-H PDAC were obtained by reviewing data of all PDAC patients from our tertiary cancer center who had undergone genomic sequencing by one commercially available platform. The resulting cohort was supplemented with MSI-H PDAC cases identified by GI oncology specialists at multiple institutions. De-identified patient data were compiled and analyzed. Results: 15 MSI-H PDAC patients were identified. 20% had stage II disease at diagnosis, 27% stage III, and 53% stage IV. 73% of patients received ICI (n=11); 40% as 1st line and 33% as 2nd line. These patients demonstrated 100% overall response rate; 45% complete response (1 pathologic CR, 4 radiographic CR) and 55% partial response. No patient that received ICI had lost response or died after a median follow-up of 18 months (range 6-89 mos). 1 patient had oligoprogression of a single hepatic lesion after 7 mos that was then irradiated; this patient retained radiographic CR for 17 subsequent mos (ongoing). In this cohort, we observe poor responses to cytotoxic chemotherapy. In total, 12 regimens were trialed among 9 patients. Overall response rate was 0%. 42% achieved disease stability, with median duration of response of 2 mos; only 2 cases maintained disease stability for &gt;5 mos. 4 patients did not receive ICI; all patients died, with a median survival of 7.5 mos. Conclusions: MSI-H PDAC represents a rare but important subtype of PDAC with unique clinical behavior. Given its rarity, large-scale analyses and trials are unlikely to be performed, making case series such as ours crucial. In our cohort, we observe impressive, durable responses to ICI, along with very poor responses to cytotoxic chemotherapy. Our data argues for consideration of ICI in any patient presenting with MSI-H PDAC, including in the first-line and neoadjuvant settings.
Racial disparities in patients with <i>TP53</i> mutated acute myeloid leukemia.
Authors: Talha Badar, Mark Robert Litzow, Rory Shallis, Maximilian Stahl, Jan Philipp Bewersdorf, Antoine N Saliba, Guilherme Sacchi de Camargo Correia, Anand Ashwin Patel, Yasmin Abaza, Guru Subramanian Guru Murthy, Adam Duvall, Madelyn Burkart, Aref Al-Kali, Neil Palmisiano, Shira Dinner, Aaron David Goldberg, Ehab L. Atallah
Journal: Journal of Clinical Oncology (2022)

e19007 Background: While clinical outcomes of patients (pts) with TP53 mutated (m) acute myeloid leukemia (AML) are dismal, subsets of pts with eligibility to curative intent therapies can do better. As racial disparities are known to impact outcome in hematological malignancies, we sought to explore disparities in TP53m AML. Methods: We conducted a multicenter study of 304 TP53m AML pts, divided into 2 groups, White (n= 240) and Black/Hispanic (n=64), to compare difference in disease characteristics and clinical outcome. We grouped Black and Hispanic together as the number of pts were small in each group and our aim was to evaluate outcome in under-represented races/ethnicities. Results: Baseline characteristics are summarized in Table. The median age of the pts was comparable between White and Black/Hispanic (p= 0.97). A significantly higher proportion of Black/Hispanic pts (23%) had diabetes mellitus when compared with White (14%) pts (p= 0.02). A higher proportion of Black/Hispanic pts had therapy-related AML (33% vs. 20%, p= 0.03), complex cytogenetics (98% vs. 87%, p= 0.003) and co-mutations (70% vs. 57%, p= 0.02). The proportion of pts who received hypomethylating agent + venetoclax (29% vs 20%, p= 0.20) or CPX-351 (22% vs 20%, p= 0.13) were comparable between White and Black/Hispanic, respectively. A higher proportion of Black/Hispanic pts received supportive care (17% vs. 4%, p= 0.002). White pts had higher rates of complete remission with or without count recovery (25% vs. 19%, p= 0.07). Only 6% of Black/Hispanic pts received allogeneic stem cell transplantation (alloHCT) compared to 16% for White pts (p= 0.01). The median event free survival was 2 months (mo) (95% CI;1.52-2.41) and 2.5 mo (95% CI:1.62-3.31) in White and Black/Hispanic pts, respectively (p= 0.71). The median overall OS was shorter for Black/Hispanic (6.37 mo [95% CI:2.88-9.85]) than for White (6.90 mo [95% CI:5.55-8.24] [p= 0.009]). Conclusions: Our study demonstrates poorer OS in Black/Hispanic pts with TP53m AML. Potential drivers of this disparity include lower alloHCT rates, higher rates of pts receiving supportive care, and higher-risk disease in Black/Hispanic pts.[Table: see text]
Real-world effectiveness of first-line maintenance olaparib in women with <i>BRCA-</i>mutated advanced ovarian cancer: U.S. retrospective cohort study.
Authors: Ramez Nassef Eskander, Naufil Alam, Grainne H. Long, Ozan Ozgoren, Will Ambler, Stephanie Volpe, Kathleen N. Moore
Journal: Journal of Clinical Oncology (2022)

5518 Background: Following cytoreductive surgery and first-line (1L) platinum based chemotherapy, 70% of patients (pts) with newly diagnosed advanced ovarian cancer (AOC) experience relapse within 3 years. 1L maintenance treatment (tx) with olaparib monotherapy, a poly (ADP-ribose) polymerase inhibitor, extended progression free survival in pts with BRCA mutated (BRCAm) AOC in the SOLO-1 (NCT01844986) randomized controlled trial (RCT). We aimed to describe real world characteristics, tx patterns, and clinical outcomes of pts with newly diagnosed, BRCAm AOC. Methods: Data were collected from 457 pts via electronic case report forms in the US. Pt eligibility criteria were positive BRCAm test result between Jan-June 2019 (6 months post 1L olaparib FDA approval), newly diagnosed AOC (no maintenance tx prior to index), aged ≥18 years, no RCT enrollment, no active neoplasia, no prior tx for metastatic/stage IV cancer. Pt follow up was until July 2021. Kaplan-Meier (KM) estimation was used for time to event analysis using progression proxies: Time to subsequent therapy and discontinuation (or death for both) from initiation of 1L maintenance olaparib monotherapy. Results: Pt mean age (±SD) at index was 62 (±10) years, 64% of pts were white and 18% African American; further clinical characteristics are in the table. 95% of pts received ≥1 pharmacological tx. At 1L, 36% of pts (156/433) received maintenance tx after chemotherapy, with 64% of pts (277/433) receiving routine surveillance (no maintenance tx). Olaparib was the most common maintenance tx (67%, 105/156), with 67% of pts (70/105) prescribed olaparib monotherapy. At 24 months, the KM model estimated 91% of pts (95% confidence interval: 82, 96) would not progress to their subsequent therapy, with a median discontinuation of olaparib monotherapy of 25.0 (interquartile range [IQR]: 21.0, not estimable) months, over a median follow-up of 22.0 (IQR: 20.6, 24.0) months. Conclusions: This real world study complements SOLO-1 RCT data by demonstrating prolonged benefit of 1L olaparib in newly diagnosed pts with BRCAm AOC in terms of lower likelihood of progression (tx switch/death). To assess real world tx effectiveness globally, data collection across further eight countries is due to be completed in 2022. [Table: see text]
Classification of esophageal adenocarcinoma into subgroups that are associated with patient survival using RNA-seq and immunohistochemistry.
Authors: Sowmya Sharma, Marjan Naeini, Lauren G Aoude, Vanessa F Bonazzi, Michael G Gartside, Kelly A Loffler, Kalpana Patel, Felicity Newell, Guy Lampe, Sandra Brosda, Janine Thomas, Mark Smithers, John Simes, David I. Watson, John Pearson, Andrew Barbour, Nic Waddell
Journal: Journal of Clinical Oncology (2022)

e16028 Background: : Prognosis of oesophageal adenocarcinoma (OAC) remains poor globally. Traditional histopathology classifications have minimal impact on clinical management and outcomes. To improve patient outcomes, prognostic and therapeutic stratification is required within this cohort of morphologically homogenous cancers. Identification and validation of candidate prognostic and therapeutic biomarkers may contribute to personalisation of therapy for patients with OAC. Methods: We used RNAseq of OAC tumour tissues to classify OAC into subgroups which were associated with patient survival and the immune infiltrate in the tumour micro-environment. We identified genes that discriminate each group and selected thirteen to perform IHC against the protein products of these genes using the same OAC samples. The IHC markers that best discriminate the immune-clusters were applied to an independent set of OAC in tissue micro-arrays (TMAs) to validate the prognostic significance of the immune-clusters. Results: Using RNA-seq we identified four candidate immune-clusters namely, immune hot, immune cold, immune suppressed and immune moderate, that correlate with progression free and overall patient survival. IHC revealed a correlation of five of thirteen of these IHC markers with the RNAseq data, and the IHC was able to corroborate the classification of OAC immune-clusters. The best markers predictive of these immune-clusters underwent IHC in an independent OAC TMA cohort to confirm the prognostic significance of these markers. The TMAs contain matched primary and nodal disease, so we will also report on the presence of the four subgroups within nodal disease. To date, two of the IHC markers are associated with survival benefit in the TMAs patient group. Conclusions: We anticipate that validating IHC markers to reliably identify the four immune-clusters of OAC will be useful in predicting prognosis, survival and therapeutic classification of OAC in precision oncology of the OAC.
Financial toxicity among patients with breast cancer in a publically funded health care system in Brazil.
Authors: Andrea Arevalo, Joao Soares Nunes, Tabatha Nakakogue, Alexandre Luders Figueiredo, Eduardo de Souza Somensi, Mariana Cararo Hauki, Marcos Daniel Weffort
Journal: Journal of Clinical Oncology (2022)

e18818 Background: The concept of financial toxicity (FT) has been used to describe the unanticipated economic damage potentially caused by cancer treatment. Currently, it has been associated with decreased health-related quality of life (QoL), treatment nonadherence and increased risk of mortality. Even in publicly funded environments as Brazilian Unified National Health System, factor such as income loss or out-of-pocket costs could become an issue for cancer care. The aim of this study was to examine the FT related to the breast cancer diagnosis and treatments in a public Brazilian tertiary hospital through Comprehensive Score for Financial Toxicity (COST) instrument. The COST is a 12-item survey scored from 0 to 44, with lower scores reflecting worse financial well-being. Methods: This cross-sectional study was conducted among breast cancer patients in active treatment for at least 6 months attending medical oncology out-patient department. Socio-demographic, clinical characteristics and a simplified assessment of QoL were collected as well as responses to COST questionnaire. Descriptive statistic and analysis of correlations between quantitative variables and scores of QoL and COST were performed. Results: A total of 100 female patients were included with median age of 53 years old. The mean time from initial diagnosis was of 49.6 months and clinical stage IV represented 46% of all cases. Prior to the cancer treatment, 48 (48%) of the patients had their own job as a main source of income. However, after the cancer diagnosis, only 9 (9%) patients keep working, 36 (36%) needed to use savings and 29 (29%) applied for a bank loan. To adjust their finances, 66 (66%) patients reduced spending on leisure. The median COST score was 18.5 (ranged from 4 to 41). According to the age, patients with ≤ 45 years old were at higher risk of suffering FT (p = 0.01). There was also an association between the COST score and QoL since the higher the FT, the lower the QoL (p &lt; 0.001). Conclusions: Patients with breast cancer are at risk of losing their work capacity, become financially dependent of other, and suffering a reduction in QoL as a result of FT. Mostly younger patients are at greater risk of FT. Despite a universal health-model, this study highlights a substantial proportion of patients who experienced FT. Therefore, further studies confirming these findings in larger groups are warranted to develop better strategies and policies to mitigate this form of toxicity.
Medical oncologists' perspectives of end-of-life care communication with racial/ethnic minority and limited English proficiency patients.
Authors: Maria De Lourdes Garcia-Jimenez, John A. Glaspy, Sidharth Anand, Anne M. Walling
Journal: Journal of Clinical Oncology (2022)

e18585 Background: Racial/ethnic minority (REM) and limited English proficiency (LEP) patients with cancer receive more intensive treatment at the end-of-life (EOL) compared to non-Hispanic whites. Various factors at the health system, patient, and provider level contribute to this disparity. While some data exists on the role of provider communication, little is known about medical oncologists' knowledge and attitudes regarding EOL care communication with REM and LEP patients with cancer. Methods: We conducted a cross-sectional, anonymous, pilot survey of medical oncology attendings and fellows at one academic center. Over 3 months, 57 individuals were invited to participate. The survey addressed 6 domains about EOL care communication with REM and LEP patients (role of language, barriers, facilitators, provider beliefs, provider communication skills, and cultural competency training). Questions used Likert scales and were modified from previously validated items when possible. Results: Of 35 individual respondents (61% response rate) 21 (60%) were male, 14 (40%) were female, and 29 (83%) were attendings. Average participant age was 42 years (range 31-60 years) and average years in practice was 9 (range 2-25 years). Twenty-three (66%) self-identified as non-Hispanic white, 11 (31%) as Asian, and 1 (3%) as other. Thirty-three (94%) reported their primary language as English and 23 (66%) reported speaking a second language. A majority (77%) strongly agreed discussing EOL care is part of an oncologist’s job and 69% strongly agreed patients with cancer, regardless of race/ethnicity or English language ability, should be engaged in EOL care discussions. Among several facilitators identified, two most highly rated as “Very Important” were eliciting patient belief systems about their disease (71%) and about death/dying (69%). However, only 14% strongly agreed they ask patients their beliefs about death/dying, and a minority strongly agreed they feel comfortable having EOL care discussions with REM (34%) and LEP (29%) patients. Importantly, 77% rated themselves at 6 or 7 (on a scale from 0 to 10, with 10 being the best) in how well they currently communicate about EOL care with REM and LEP patients, 74% reported wanting to be at 8 or 9 in 6 months, and 89% completely or somewhat agreed with wanting help to improve. Conclusions: Our results suggest there is conceptual understanding among academic medical oncologists of the need to engage all patients in EOL care discussions and elicit patient belief systems on the topic. Though there is lack of comfort in having EOL care discussions with REM and LEP patients, and infrequent inquiry about patient belief systems, there is also motivation to improve communication skills in this area. Interventions that foster medical oncologists' comfort and skills in cross-cultural, language non-congruent communication about EOL care are needed.